Investigating obesity as a risk factor for influenza-like illness during the 2009 H1N1 influenza pandemic using the Health Survey for England.

BACKGROUND: Following the 2009 H1N1 influenza pandemic, obesity was shown to be associated with severe influenza outcomes. It remains unclear whether obesity was a risk factor for milder influenza-like illness (ILI). OBJECTIVES: To determine whether obesity was associated with an increased risk of self-reported ILI during the 2009 H1N1 influenza pandemic using Health Survey for England (HSE) 2010 cross-sectional data. METHODS: This study used HSE data collected from English households between January and December 2010. Weight and height measurements were taken by trained fieldworkers to determine obesity. ILI was defined as a positive response to the question "Have you had a flu-like illness where you felt feverish and had a cough or sore throat?" with illness occurring between May and December 2009. Multivariable logistic regression was used to evaluate the association between obesity and ILI. RESULTS: The study comprised 8407 participants (6984 adults, 1436 children), among whom 24.7% (95% CI: 23.6-25.9) were classified as obese. Of obese participants, 12.8% (95% CI: 11.1-14.8) reported ILI compared to 11.8% (95% CI: 10.8-12.8) of non-obese participants. The adjusted OR for ILI associated with obesity was 1.16 (95% CI: 0.98-1.38, P=.093). For adults and children, the adjusted ORs were 1.16 (95% CI: 0.97-1.38, P=.101) and 1.26 (95% CI: 0.72-2.21, P=.422), respectively. CONCLUSION: Household survey data showed no evidence that obesity was associated with an increase in self-reported ILI during the 2009 H1N1 influenza pandemic in England. Further studies using active prospective ILI surveillance combined with laboratory reporting would reduce bias and improve accuracy of outcome measurements

Population-level susceptibility, severity and spread of pandemic influenza: design of, and initial results from, a pre-pandemic and hibernating pandemic phase study using cross-sectional data from the Health Survey for England (HSE)

Background Assessing severity and spread of a novel influenza strain at the start of a pandemic is critical for informing a targeted and proportional response. It requires community-level studies to estimate the burden of infection and disease. Rapidly initiating such studies in a pandemic is difficult. The study aims to establish an efficient system allowing real-time assessment of population susceptibility, spread of infection and clinical attack rates in the event of a pandemic. Methods We developed and appended additional survey questions and specimen collection to the Health Survey for England (HSE) – a large, annual, rolling nationally representative general population survey recruiting throughout the year – to enable rapid population-based surveys of influenza infection and disease during a pandemic. Using these surveys we can assess the spread of the virus geographically, by age and through time. The data generated can also provide denominators for national estimates of case fatality and hospitalisation rates.Phase 1: we compared retrospectively collected HSE illness rates during the first two infection waves of the 2009 pandemic with the Flu Watch study (a prospective community cohort). Monthly and seasonal age-specific rates of illness and proportion vaccinated were compared.Phase 2: we piloted blood specimen and data collection alongside the 2012–13 HSE. We are developing laboratory methods and protocols for real-time serological assays of a novel pandemic influenza virus using these specimens, and automated programmes for analysing and reporting illness and infection rates.Phase 3: during inter-pandemic years, the study enters a holding phase, where it is included in the yearly HSE ethics application and planning procedures, allowing rapid triggering in a pandemic.Phase 4: once retriggered, the study will utilise the methods developed in phase 2 to monitor the severity and spread of the pandemic in real time. Results Phase 1: the rates of reported illness during the first two waves in the HSE underestimated the community burden as measured by Flu Watch, but the patterns of illness by age and time were broadly comparable. The extent of underestimation was greatest for HSE participants interviewed later in the year compared with those interviewed closer to the pandemic. Vaccine uptake in the HSE study was comparable to independent national estimates and the Flu Watch study.Phases 2 and 3: illness data and serological samples from 2018 participants were collected in the 2012–13 HSE and transferred to the University College London Hospital. In the 2013 HSE and onwards, this project was included in the annual HSE ethics and planning rounds. Conclusions The HSE’s underestimation of illness rates during the first two waves of the pandemic is probably due to recall bias and the limitation of being able to report only one illness when multiple illnesses per season can occur. Changes to the illness questions (reporting only recent illnesses) should help minimise these issues. Additional prospective follow-up could improve measurement of disease incidence. The representative nature of the HSE allows accurate measurements of vaccine uptake. Study registration This study is registered as ISRCTN80214280. Funding This project was funded by the NIHR Public Health Research programme and will be published in full inPublic Health Research; Vol. 3, No. 6. See the NIHR Journals Library website for further project information

Black, Asian and Minority Ethnic groups in England are at increased risk of death from COVID-19: indirect standardisation of NHS mortality data

Background: International and UK data suggest that Black, Asian and Minority Ethnic (BAME) groups are at increased risk of infection and death from COVID-19. We aimed to explore the risk of death in minority ethnic groups in England using data reported by NHS England. Methods: We used NHS data on patients with a positive COVID-19 test who died in hospitals in England published on 28th April, with deaths by ethnicity available from 1st March 2020 up to 5pm on 21 April 2020. We undertook indirect standardisation of these data (using the whole population of England as the reference) to produce ethnic specific standardised mortality ratios (SMRs) adjusted for age and geographical region. Results: The largest total number of deaths in minority ethnic groups were Indian (492 deaths) and Black Caribbean (460 deaths) groups. Adjusting for region we found a lower risk of death for White Irish (SMR 0.52; 95%CIs 0.45-0.60) and White British ethnic groups (0.88; 95%CIs 0.86-0.0.89), but increased risk of death for Black African (3.24; 95%CIs 2.90-3.62), Black Caribbean (2.21; 95%CIs 2.02-2.41), Pakistani (3.29; 95%CIs 2.96-3.64), Bangladeshi (2.41; 95%CIs 1.98-2.91) and Indian (1.70; 95%CIs 1.56-1.85) minority ethnic groups. Conclusion: Our analysis adds to the evidence that BAME people are at increased risk of death from COVID-19 even after adjusting for geographical region, but was limited by the lack of data on deaths outside of NHS settings and ethnicity denominator data being based on the 2011 census. Despite these limitations, we believe there is an urgent need to take action to reduce the risk of death for BAME groups and better understand why some ethnic groups experience greater risk. Actions that are likely to reduce these inequities include ensuring adequate income protection, reducing occupational risks, reducing barriers in accessing healthcare and providing culturally and linguistically appropriate public health communications

Seasonality and immunity to laboratory-confirmed seasonal coronaviruses (HCoV-NL63, HCoV-OC43, and HCoV-229E): results from the Flu Watch cohort study

Background: There is currently a pandemic caused by the novel coronavirus SARS-CoV-2. The intensity and duration of this first wave in the UK may be dependent on whether SARS-CoV-2 transmits more effectively in the winter than the summer and the UK Government response is partially built upon the assumption that those infected will develop immunity to reinfection in the short term. In this paper we examine evidence for seasonality and immunity to laboratory-confirmed seasonal coronavirus (HCoV) from a prospective cohort study in England. Methods: In this analysis of the Flu Watch cohort, we examine seasonal trends for PCR-confirmed coronavirus infections (HCoV-NL63, HCoV-OC43, and HCoV-229E) in all participants during winter seasons (2006-2007, 2007-2008, 2008-2009) and during the first wave of the 2009 H1N1 influenza pandemic (May-Sep 2009). We also included data from the pandemic and �post-pandemic� winter seasons (2009-2010 and 2010-2011) to identify individuals with two confirmed HCoV infections and examine evidence for immunity against homologous reinfection. Results: We tested 1,104 swabs taken during respiratory illness and detected HCoV in 199 during the first four seasons. The rate of confirmed HCoV infection across all seasons was 390 (95% CI 338-448) per 100,000 person-weeks; highest in the Nov-Mar 2008/9 season at 674 (95%CI 537-835). The highest rate was in February at 759 (95% CI 580-975). Data collected during May-Sep 2009 showed there was small amounts of ongoing transmission, with four cases detected during this period. Eight participants had two confirmed infections, of which none had the same strain twice. Conclusion: Our results provide evidence that HCoV infection in England is most intense in winter, but that there is a small amount of ongoing transmission during summer periods. We found some evidence of immunity against homologous reinfection.</ns3:p

Public activities preceding the onset of acute respiratory infection syndromes in adults in England - implications for the use of social distancing to control pandemic respiratory infections.

Background: Social distancing measures may reduce the spread of emerging respiratory infections however, there is little empirical data on how exposure to crowded places affects risk of acute respiratory infection. Methods: We used a case-crossover design nested in a community cohort to compare self-reported measures of activities during the week before infection onset and baseline periods. The design eliminates the effect of non-time-varying confounders. Time-varying confounders were addressed by exclusion of illnesses around the Christmas period and seasonal adjustment.  Results: 626 participants had paired data from the week before 1005 illnesses and the week before baseline. Each additional day of undertaking the following activities in the prior week was associated with illness onset: Spending more than five minutes in a room with someone (other than a household member) who has a cold (Seasonally adjusted OR 1·15, p=0·003); use of underground trains (1·31, p=0·036); use of supermarkets (1·32, p<0·001); attending a theatre, cinema or concert (1·26, p=0·032); eating out at a café, restaurant or canteen (1·25, p=0·003); and attending parties (1·47, p<0·001). Undertaking the following activities at least once in the previous week was associated with illness onset: using a bus, (aOR 1.48, p=0.049), shopping at small shops (1.9, p<0.002) attending a place of worship (1.81, p=0.005).    Conclusions: Exposure to potentially crowded places, public transport and to individuals with a cold increases risk of acquiring circulating acute respiratory infections. This suggests social distancing measures can have an important impact on slowing transmission of emerging respiratory infections

Hand Hygiene Practices and the Risk of Human Coronavirus Infections in a UK Community Cohort.

Background: Hand hygiene may mitigate the spread of COVID-19 in community settings; however, empirical evidence is limited. Given reports of similar transmission mechanisms for COVID-19 and seasonal coronaviruses, we investigated whether hand hygiene impacted the risk of acquiring seasonal coronavirus infections. Methods: Data were drawn from three successive winter cohorts (2006-2009) of the England-wide Flu Watch study.  Participants ( n=1633) provided baseline estimates of hand hygiene behaviour. Coronavirus infections were identified from nasal swabs using RT-PCR. Poisson mixed models estimated the effect of hand hygiene on personal risk of coronavirus illness, both unadjusted and adjusted for confounding by age and healthcare worker status. Results: Moderate-frequency handwashing (6-10 times per day) predicted a lower personal risk of coronavirus infection (adjusted incidence rate ratio (aIRR) =0.64, p=0.04). There was no evidence for a dose-response effect of handwashing, with results for higher levels of hand hygiene (>10 times per day) not significant (aIRR =0.83, p=0.42). Conclusions: This is the first empirical evidence that regular handwashing can reduce personal risk of acquiring seasonal coronavirus infection. These findings support clear public health messaging around the protective effects of hand washing in the context of the current COVID-19 pandemic

Seasonality and immunity to laboratory-confirmed seasonal coronaviruses (HCoV-NL63, HCoV-OC43, and HCoV-229E): results from the Flu Watch cohort study.

Background: There is currently a pandemic caused by the novel coronavirus SARS-CoV-2. The intensity and duration of this first and second waves in the UK may be dependent on whether SARS-CoV-2 transmits more effectively in the winter than the summer and the UK Government response is partially built upon the assumption that those infected will develop immunity to reinfection in the short term. In this paper we examine evidence for seasonality and immunity to laboratory-confirmed seasonal coronavirus (HCoV) from a prospective cohort study in England. Methods: In this analysis of the Flu Watch cohort, we examine seasonal trends for PCR-confirmed coronavirus infections (HCoV-NL63, HCoV-OC43, and HCoV-229E) in all participants during winter seasons (2006-2007, 2007-2008, 2008-2009) and during the first wave of the 2009 H1N1 influenza pandemic (May-Sep 2009). We also included data from the pandemic and 'post-pandemic' winter seasons (2009-2010 and 2010-2011) to identify individuals with two confirmed HCoV infections and examine evidence for immunity against homologous reinfection. Results: We tested 1,104 swabs taken during respiratory illness and detected HCoV in 199 during the first four seasons. The rate of confirmed HCoV infection across all seasons was 390 (95% CI 338-448) per 100,000 person-weeks; highest in the Nov-Mar 2008/9 season at 674 (95%CI 537-835) per 100,000 person-weeks. The highest rate was in February at 759 (95% CI 580-975) per 100,000 person-weeks. Data collected during May-Sep 2009 showed there was small amounts of ongoing transmission, with four cases detected during this period. Eight participants had two confirmed infections, of which none had the same strain twice. Conclusion: Our results provide evidence that HCoV infection in England is most intense in winter, but that there is a small amount of ongoing transmission during summer periods. We found some evidence of immunity against homologous reinfection

Natural T cell–mediated protection against seasonal and pandemic Influenza: results of the Flu Watch cohort study

Rationale: A high proportion of influenza infections are asymptomatic. Animal and human challenge studies and observational studies suggest T cells protect against disease among those infected, but the impact of T-cell immunity at the population level is unknown. Objectives: To investigate whether naturally preexisting T-cell responses targeting highly conserved internal influenza proteins could provide cross-protective immunity against pandemic and seasonal influenza. Methods: We quantified influenza A(H3N2) virus–specific T cells in a population cohort during seasonal and pandemic periods between 2006 and 2010. Follow-up included paired serology, symptom reporting, and polymerase chain reaction (PCR) investigation of symptomatic cases. Measurements and Main Results: A total of 1,414 unvaccinated individuals had baseline T-cell measurements (1,703 participant observation sets). T-cell responses to A(H3N2) virus nucleoprotein (NP) dominated and strongly cross-reacted with A(H1N1)pdm09 NP (P < 0.001) in participants lacking antibody to A(H1N1)pdm09. Comparison of paired preseason and post-season sera (1,431 sets) showed 205 (14%) had evidence of infection based on fourfold influenza antibody titer rises. The presence of NP-specific T cells before exposure to virus correlated with less symptomatic, PCR-positive influenza A (overall adjusted odds ratio, 0.27; 95% confidence interval, 0.11–0.68; P = 0.005, during pandemic [P = 0.047] and seasonal [P = 0.049] periods). Protection was independent of baseline antibodies. Influenza-specific T-cell responses were detected in 43%, indicating a substantial population impact. Conclusions: Naturally occurring cross-protective T-cell immunity protects against symptomatic PCR-confirmed disease in those with evidence of infection and helps to explain why many infections do not cause symptoms. Vaccines stimulating T cells may provide important cross-protective immunity

Black, Asian and Minority Ethnic groups in England are at increased risk of death from COVID-19: indirect standardisation of NHS mortality data.

Background: International and UK data suggest that Black, Asian and Minority Ethnic (BAME) groups are at increased risk of infection and death from COVID-19. We aimed to explore the risk of death in minority ethnic groups in England using data reported by NHS England. Methods: We used NHS data on patients with a positive COVID-19 test who died in hospitals in England published on 28th April, with deaths by ethnicity available from 1st March 2020 up to 5pm on 21 April 2020. We undertook indirect standardisation of these data (using the whole population of England as the reference) to produce ethnic specific standardised mortality ratios (SMRs) adjusted for age and geographical region. Results: The largest total number of deaths in minority ethnic groups were Indian (492 deaths) and Black Caribbean (460 deaths) groups. Adjusting for region we found a lower risk of death for White Irish (SMR 0.52; 95%CIs 0.45-0.60) and White British ethnic groups (0.88; 95%CIs 0.86-0.0.89), but increased risk of death for Black African (3.24; 95%CIs 2.90-3.62), Black Caribbean (2.21; 95%CIs 2.02-2.41), Pakistani (3.29; 95%CIs 2.96-3.64), Bangladeshi (2.41; 95%CIs 1.98-2.91) and Indian (1.70; 95%CIs 1.56-1.85) minority ethnic groups. Conclusion: Our analysis adds to the evidence that BAME people are at increased risk of death from COVID-19 even after adjusting for geographical region, but was limited by the lack of data on deaths outside of NHS settings and ethnicity denominator data being based on the 2011 census. Despite these limitations, we believe there is an urgent need to take action to reduce the risk of death for BAME groups and better understand why some ethnic groups experience greater risk. Actions that are likely to reduce these inequities include ensuring adequate income protection, reducing occupational risks, reducing barriers in accessing healthcare and providing culturally and linguistically appropriate public health communications

Symptom reporting, healthcare-seeking behaviour and antibiotic use for common infections: protocol for Bug Watch, a prospective community cohort study.

INTRODUCTION: Antimicrobial resistance is a significant worldwide problem largely driven by selective pressure exerted through antibiotic use. Preserving antibiotics requires identification of opportunities to safely reduce prescriptions, for example in the management of mild common infections in the community. However, more information is needed on how infections are usually managed and what proportion lead to consultation and antibiotic use. The aim of this study is to quantify consultation and prescribing patterns in the community for a range of common acute infection syndromes (respiratory, gastrointestinal, skin/soft tissue, mouth/dental, eye and urinary tract). This will inform development of interventions to improve antibiotic stewardship as part of a larger programme of work, Preserving Antibiotics through Safe Stewardship. METHODS AND ANALYSIS: This will be an online prospective community cohort study in England. We will invite 19 510 adults who previously took part in a nationally representative survey (the Health Survey for England) and consented to be contacted about future studies. Adults will also be asked to register their children. Data collection will consist of a baseline registration survey followed by weekly surveys sent by email for 6 months. Weekly surveys will collect information on symptoms of common infections, healthcare-seeking behaviour and use of treatments including antibiotics. We will calculate the proportions of infection syndromes that lead to General Practitioner consultation and antibiotic prescription. We will investigate how healthcare-seeking and treatment behaviours vary by demographics, social deprivation, infection profiles and knowledge and attitudes towards antibiotics, and will apply behavioural theory to investigate barriers and enablers to these behaviours. ETHICS AND DISSEMINATION: This study has been given ethical approval by the University College London Research Ethics Committee (ID 11813/001). Each participant will provide informed consent upon registration. We will disseminate our work through publication in peer-reviewed academic journals. Anonymised data will be made available through the UK Data Service (https://www.ukdataservice.ac.uk/)